Neutrophil NETs in reproduction: from infertility to preeclampsia and the possibility of fetal loss.

Hahn, S
·
Giaglis, S
·
Hoesli, I
·
Hasler, P

Abstract: The intention of this review is to provide an overview of the potential role of neutrophil extracellular traps (NETs) in mammalian reproduction. Neutrophil NETs appear to be involved in various stages of the reproductive cycle, starting with fertility and possibly ending with fetal loss. The first suggestion that NETs may play a role in pregnancy-related disorders was in preeclampsia, where vast numbers were detected in the intervillous space of affected placentae. The induction of NETosis involved an auto-inflammatory component, mediated by the increased release of placental micro-debris in preeclampsia. This report was the first indicating that NETs may be associated with a human pathology not involving infection. Subsequently, NETs have since then been implicated in bovine or equine infertility, in that semen may become entrapped in the female reproductive tract during their passage to the oocyte. In this instance interesting species-specific differences are apparent, in that equine sperm evade entrapment via expression of a DNAse-like molecule, whereas highly motile bovine sperm, once free from seminal plasma (SP) that promotes interaction with neutrophils, appear impervious to NETs entrapment. Although still in the realm of speculation it is plausible that NETs may be involved in recurrent fetal loss mediated by anti-phospholipid antibodies, or perhaps even in fetal abortion triggered by infections with microorganisms such as L. monocytogenes or B. abortus.

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Publication Date: 2012-11-27 PubMed ID: 23205021PubMed Central: PMC3506920DOI: 10.3389/fimmu.2012.00362Google Scholar: Lookup

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This article reviews the possible role of neutrophil extracellular traps (NETs) in the complex process of mammalian reproduction, from fertility to potential fetal loss, with a focus on their connection to certain pregnancy-related disorders like preeclampsia and infertility.

Role of Neutrophil Extracellular Traps (NETs) in Reproduction

Neutrophil extracellular traps, or NETs, are web-like structures, released by neutrophils, a type of white blood cell. They are primarily recognized for their role in trapping and killing pathogens.

The paper investigates the potential involvement of NETs in various components of the reproductive cycle, beginning with fertility and potentially culminating in fetal loss.
The first indication that NETs might have a role in pregnancy-related disorders came from a study on preeclampsia. This condition is characterised by high blood pressure during pregnancy and can lead to severe complications for both mother and child. A significantly higher number of NETs were found in the intervillous space of affected placentae in preeclampsia patients.
The activation of NETs, referred as NETosis, occurring in preeclampsia was revealed to involve an auto-inflammatory component, driven by an increased release of placental micro-debris.
This was the first time that NETs were linked to a human pathology that does not revolve around infection.

Cross-Species Comparison of NETs Interaction With Sperm

NETs also appear to play a role in bovine and equine infertility.

The researchers noted an interesting phenomenon wherein semen could become ensnared in the female reproductive tract by NETs, potentially preventing it from reaching the oocyte and causing infertility.
However, there were significant species-specific differences. Equine sperm, for instance, can avoid this entrapment through the expression of a DNAse-like molecule.
Conversely, bovine sperm seemed immune to NETs entrapment once they were free from the seminal plasma that promotes interaction with neutrophils.

Potential Role of NETs in Fetal Loss

The researchers explore the possibility of the implication of NETs in recurrent fetal loss and abortion.

There’s speculation that NETs may play a part in recurrent fetal loss mediated by anti-phospholipid antibodies, which, in some instances can cause complications in pregnancy.
The review also suggests the possibility of NETs being involved in fetal abortion triggered by infections with certain microorganisms like L. monocytogenes or B. abortus.

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APA

Hahn S, Giaglis S, Hoesli I, Hasler P. (2012). Neutrophil NETs in reproduction: from infertility to preeclampsia and the possibility of fetal loss. Front Immunol, 3, 362. https://doi.org/10.3389/fimmu.2012.00362

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Frontiers in immunology

ISSN: 1664-3224

NlmUniqueID: 101560960

Country: Switzerland

Language: English

Volume: 3

Pages: 362

PII: 362

Researcher Affiliations

Hahn, Sinuhe

Department of Biomedicine, University of Basel/Laboratory for Prenatal Medicine, University Clinics, University Women's Hospital Basel, Switzerland.

Giaglis, Stavros

Hoesli, Irene

Hasler, Paul

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Citations

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